Staphylococcus aureus is a ubiquitous pathogen, and causes infections of the skin, bloodstream, lung, and other body sites. Community-acquired methicillin resistant S. aureus (CA-MRSA) infections, which were previously extremely rare, are now occurring commonly worldwide. CA-MRSA is the most common cause of skin infection in many locales in the U.S., including Southern California. CA-MRSA strains are notable for their ability to spread in closed settings and cause recurrent infections among healthy persons. Management of recurrent CA-MRSA infection is challenging and optimal prevention strategies are undefined. Many experts recommend topical agents that decontaminate the body and/or anterior nares. Others suggest environmental decontamination to help control recurrences and transmission within households. However, there are no data that quantify the efficacy and safety of these approaches. We will conduct a multi-center clinical trial to compare the efficacy and safety of body and environmental decolonization regimens in the prevention of CA-MRSA infection. The study population will comprise of persons suffering from recurrent CA-MRSA infection. This investigation will partner investigators with extensive experience studying CA-MRSA infection with investigators from Kaiser Permanente Southern California, a large Health Maintenance Organization that is a leader in the use of electronic medical records. For this clinical trial, all subjects will be randomized in a 2 x 2 design to test: 1) chlorhexidine body washes plus nasal mupirocin ointment vs. usual care, and 2) environmental cleansing with ethanol spray and aggressive laundering vs. no environmental cleansing. We will also conduct complementary investigations, including studying the interventions'efficacy at preventing infections in household members, modeling oredictors of recurrent CA-MRSA infection, and measuring pharmaco-economic outcomes. We will also examine strain relatedness of colonizing and infecting CA-MRSA strains to better understand colonization dynamics within households. Our clinical trial will forward our understanding of the benefit of decolonization regimens at preventing A-MRSA infection. Additionally, our studies will advance our understanding of the pathogenesis and scope of recurrent CA-MRSA infection.